Preclinical evaluation of recombinant herpes simplex virus oHSV2 in colorectal cancer / 中国肿瘤临床

Objective:To investigate therapeutic efficacy and mechanisms of action of oncolytic agent derived from herpes simplex virus type 2 (oHSV2) in a xenograft mouse model bearing CT26 colorectal cancer. Methods:BALB/c mice were subcutaneously inoculated with CT26 cells to establish a xenograft mouse model of colorectal cancer. 1) After intratumoral administration of oHSV2, enzyme-linked im-munosorbent assay was used to determine granulocyte-macrophage colony-stimulating factor (GM-CSF) expression levels in the blood. 2) Model mice were divided into three groups:PBS group (negative control), oHSV2 group, and 5-fluorouracil (5-FU) group (positive control). After drug administration, drug effectiveness was evaluated on the basis of weight, tumor volume, general state, and survival time. 3) Cells from the draining lymph nodes (TDLN) and tumor were surgical y removed and used to quantify mature dendritic cel s (DCs) and T lym-phocytes by flow cytometry. Result:1) In the CT26 xenograft model, level of GM-CSF continuously elevated. At day 8, peak value was attained in the blood at concentration of 3150±327.1 pg/mL. Then, GM-CSF expression gradually reduced as time progressed. 2) In in vivo study, both oHSV2 and 5-FU exerted antitumor effects relative to PBS group (50 days vs. 36 days, P0.05). Skin of virus injection region did not present necrosis and ulceration. 3) In the TDLN, the frequency of DC was increased when treated with oHSV2 compared with the control group (6.49%vs. 3.73%, P<0.01). Similarly, the percentage of CD4+and CD8+T-cel s from the oHSV2-treated group was signifcantly higher than mock-treated tumors (15%vs. 8.57%, P<0.01;8.19%vs. 5.15%, P<0.01). However, number of cells in the 5-FU group were significantly reduced with respect to that of the negative group (al P<0.01). Conclusion:oHSV2 exerted potent antitumor effects in a murine colorectal cancer model. Compared with 5-FU, oHSV2 treatment caused fewer side effects. Such antitumor effect may be induced by stimulation of immune activity by GM-CSF production.

Advances in virus-based therapies for colorectal cancer / 中国肿瘤临床

Virus-based anti-tumor therapies are novel biological treatments. Viral vectors can infect tumors to kill cancers directly (on-colysis), act as cancer vaccines to activate the immune system, and deliver genes with anti-tumor activity to the cancer cells. Genetic engineering has been applied to viruses to achieve more specific and efficient cancer treatment. Simultaneously, a reasonable combi-nation of viral vectors and existing anti-tumor therapy can improve the therapeutic effect. Consequently, virus-based therapy is expect-ed to serve as an effective anti-tumor strategy. We reviewed recent studies on the anti-tumor viral therapy of colorectal carcinoma.

Meta-analysis comparing robotic right colectomy with laparoscopic right colectomy on clinical short-term outcomes / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the clinical short-term safety and efficacy between robotic right colectomy (RRC) and laparoscopic right colectomy(LRC) with meta-analysis.</p><p><b>METHODS</b>A search of the Medline, Embase, Ovid, CNKI and WANFANG databases was performed for studies comparing clinical or oncologic outcomes of RRC with LRC before July 2014. The RevMan 5.2 software was used for meta-analysis. The operative time, estimated blood loss, length of hospital stay, conversion rate to open surgery, postoperative complications and related outcomes were evaluated.</p><p><b>RESULTS</b>Six studies including 217 RRC cases and 400 conventional LRC cases were enrolled and analyzed. The meta-analysis showed that RRC had longer operative time (MD=48.05, 95% CI: 26.52 to 69.57, P<0.01), less estimated blood loss (MD=-17.74, 95% CI: -28.32 to -7.16, P=0.01), faster postoperative intestinal peristalsis recovery (MD=-0.79, 95% CI: -1.10 to -0.48, P<0.01), lower postoperative overall complications (OR=0.63, 95% CI: 0.42 to 0.93, P=0.02). Conversion rate and postoperative hospital stay between the two groups were not significantly different (all P>0.05).</p><p><b>CONCLUSION</b>Compared to LRC, RRC is associated with less estimated blood loss, faster postoperative intestinal peristalsis recovery, lower postoperative overall complications, and longer operative time.</p>

Expression of high mobility group box-1 in colorectal cancer and its clinical significance / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression level of high mobility group box-1 (HMGB1) in human colorectal cancer and its relation with different clinicopathological characteristics and prognosis of colorectal cancer patients.</p><p><b>METHODS</b>Immunohistochemical method was used to detect the HMGB1 expression in tissue samples of 86 colorectal cancer patients and 32 normal colorectal tissue samples. Positive rates of HMGB1 expression were compared among different clinicopathological characteristics. Relation of HMGB1 expression with survival was analyzed.</p><p><b>RESULTS</b>HMGB1 expression was mainly in colorectal cancer cell nucleus, with a few appearance of co-expression in nucleus and cytoplasm. Positive rate of HMGB1 expression in normal tissues was significantly lower than that in colorectal cancers [9.4% (3/32) vs. 66.3% (57/86), P=0.000], and it was much higher in large cancers, lower differentiation, invasion to outside serosa, advanced clinical stage and lymph node metastasis (all P<0.05), but was similar in terms of age and gender (P>0.05). Survival analysis showed that 3-year survival rate of patients with positive HMGB1 expression was significantly lower as compared to those with negative HMGB1 expression (56.1% vs. 85.7%, P=0.021), meanwhile it was significantly lower in patients with co-expression in nucleus and cytoplasm as compared to those with simple nuclear expression (41.4% vs. 75.0%, P=0.013).</p><p><b>CONCLUSIONS</b>HMGB1 expression in colorectal cancer is high, and its positive rate increases with the low differentiation, invasion and metastasis. HMGB1 co-expression in nucleus and cytoplasm indicates poor prognosis of colorectal cancer patients.</p>

The relationships of HGF and c-Met expression with liver metastasis of gastric cancer / 实用医学杂志

Objective To investigate the relationships of HGF , c-Met expression and clinicopathological factors with liver metastasis of gastric cancer. Methods The tissues of primary tumors and corresponding liver metastasis were collected to detect the expression of HGF and c-Met by immunohistochemistry. Results The positive rates of HGF in the experimental group and the control group were 68% and 60%, respectively , with significant differences between two groups. The positive rates of c-Met of the two groups were 86% and 68%, respectively, with a significant difference between two groups. Lymph node metastasis, high expression of HGF and c-Met were significantly associated with liver metastasis of gastric cancer. The depth of invasion of bowel wall and degree of differentiation were not associated with the liver metastasis of gastric cancer. Conclusion High expressions of HGF and c-Met are closely associated with the liver metastasis mechanism of gastric cancer. The c-Met might be a useful indicator of liver metastasis in patients with gastric cancer.

Silencing HMGB1 expression by lentivirus-mediated small interfering RNA (siRNA) inhibits the proliferation and invasion of colorectal cancer LoVo cells in vitro and in vivo / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To inquire into the influence of silencing HMGB1 expression by small interfering RNA (siRNA) on cell growth, proliferation, invasion and metastasis of colorectal cancer LoVo cells both in vitro and in vivo.</p><p><b>METHODS</b>Lentivirus-mediated HMGB1 siRNA was transfected into LoVo cells to silence the HMGB1 expression. The HMGB1 mRNA and protein expression after siRNA transfection was detected by RT-PCR and Western blot. MTT assay was used to observe the cell proliferation and to draw a growth curve. Cell cycle was measured by flow cytometry. The ability of invasion and speed of cell migration were evaluated by transwell chamber invasion and cell scratch assay. The influence of HMGB1 silencing on the proliferation of LoVo cells in vivo was observed in LoVo tumor-bearing nude mice.</p><p><b>RESULTS</b>Lentivirus-mediated siRNA was successfully transfected into colorectal cancer cell line LoVo. The expression of HMGB1 mRNA and protein in the HMGB1-siRNA group were 0.24±0.04 and 0.21±0.03, respectively. Compared with the HMGB1-siRNA-Neg group (0.82±0.13, 1.15±0.18) and control group (0.93±0.15, 1.21±0.20), the difference was significant (P<0.05). MTT assay showed that the cell proliferation in the HMGB1-siRNA group was significantly inhibited when compared with that in the HMGB1-siRNA-Neg group and control group (P<0.05). Flow cytometry showed that the proliferation index (PI) of HMGB1-siRNA group was 38.27±1.32, significantly lower than 54.66±1.74 in the HMGB1-siRNA-Neg group and 57.43±1.29 in the control group (P<0.05). The transwell assay showed that the number of penetrated cells in the HMGB1-siRNA group was 14.0±3.5, significantly lower than 51.0±6.7 in the HMGB1-siRNA-Neg group and 68.0±5.3 in the control group (P<0.05). Similarly, the scrape wound recovered significantly slower in the HMGB1-siRNA group (83.61±23.21) µm than that in the other two groups (202.86±46.46) µm and (214.58±57.38) µm(P<0.05). The nude mouse xenograft tumor experiment showed that the final tumor volume was (521±34) mm3 in the HMGB1-siRNA group, significantly smaller than that in the HMGB1-siRNA-Neg group of (763±46) mm3 and control group of (802±51) mm3 (P<0.05).</p><p><b>CONCLUSIONS</b>Lentivirus-mediated HMGBl-siRNA can effectively inhibit the HMGB1 expression in colorectal cancer LoVo cells both in vitro and in vivo. HMGB1 gene silencing can slow the growth of colorectal cancer cells, extend the cell proliferation cycle, decrease their invasion and migration, and significantly inhibit the growth of xenograft tumor in nude mice.</p>

Association of expression of HGF and its receptor c-Met to primary colorectal cancers with synchronous liver metastasis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the association between expression of hepatocyte growth factor(HGF) and its receptor c-Met and primary colorectal cancers with synchronous liver metastases.</p><p><b>METHODS</b>A total of 30 colorectal cancer patients with synchronous liver metastasis underwent radical resection of primary cancer and liver cancer in our hospital from June 2001 to June 2010. According to lymphatic metastasis, patients were divided into group A(T1~T4N1~N2M1, n=21) and group B(T1~T4N0M1, n=9). Twenty-one matched T1~T4N1~N2M0 and 21 T1~T4N0M0 patients were used as the controls of group A. Nine matched T1~T4N0M0 patients were used as the controls of group B. Expressions of HGF and c-Met in tissues of primary loci, liver loci and metastatic loci were detected by immunohistochemistry.</p><p><b>RESULTS</b>In primary loci of group A, the positive rate of HGF was significantly higher than that of T1~T4N1~N2M0 and T1~T4N0M0 controls [71%(15/21) vs. 43%(9/21), 19%(4/21), all P<0.05]. The positive rate of c-MET[90%(19/21)] was significantly higher compared to T1~T4N0M0 control[43%(9/21), P<0.05], while not significantly different compared to T1~T4N1~N2M0 control[86%(18/21)]. In primary loci of group B, positive rates of HGF and c-MET were not significantly different as compared to T1~T4N0M0 control[6/9 vs. 5/9, P>0.05; 8/9 vs. 6/9, P>0.05]. Concordance of HGF and c-MET expression in group A among primary loci, lymphatic metastatic loci and hepatic metastatic loci was 81%(17/21) and 76%(16/21).</p><p><b>CONCLUSION</b>HGF-c-Met may play a role in colorectal cancer patients with synchronous liver metastasis who have regional lymphatic metastasis, and may have few effect on colorectal cancer with synchronous liver metastasis without corresponding lymphatic metastasis.</p>

Research progress in Caveolin-1s' role in gastrointestinal cancer / 国际肿瘤学杂志

Caveolin-1 is an important surface structural marker of Caveolae. It is closely involved in the proliferation, apoptosis, invasion, metastasis, angiogenesis, signal transduction and multi-drug resistance of various tumor cells. Recent studies have found that altered Caveolin-1 expression has dual roles, as a tumor suppressor and promoter, in different stages of gastrointestinal cancer development and progression. The exact mechanisms of Caveolin-1s' involvement in the development of gastrointestinal cancer remain to be clarified and have attracted the attention of a lot of researchers.

Clinical value of ~(18)F-FDG PET/CT in postoperative diagnosis of gastrointestinal malignant tumor / 中国现代普通外科进展

Objective: To evaluate the clinical value of 18F-FDG PET/CT in diagnosing the recurrence or metastasis of the postoperative patients with gastrointestinal malignant tumor. Methods: Sixty-eight postoperative patients with gastrointestinal malignant tumor were studied with 18F-FDG PET/CT, and serum CEA and CA19-9 were assayed. Results: Thirty-seven patients were found to be recurrent or metastatic. The sensitivity and specificity of PET/CT detection were 97.3% and 96.8%,and the positive rates of PET/CT combined with CEA and CA19-9 were 100% and 97.8%.Conclusion: PET/CT has a higher sensitivity and specificity than tumor marker detection in assessment of recurrence and metastasis.